This proposal will continue to characterize the behavioral effects of arginine vasopressin (AVP) and to explore its mechanism and site of action. Based on studies with AVP analogs, one of which is a vasopressor AVP antagonist peptide, our hypothesis is that peripherally derived (pituitary) AVP alters behavior secondary to its peripheral, physiological effects, but that central AVP has behavioral actions that are separate and of unknown mechanism. An interoceptive stimulus (osmotic challenge with hypertonic saline), known to release AVP, produced behavioral effects similar to administration of exogenous AVP and these behavioral effects were reversed by systemic administration of the AVP antagonist peptide. Studies are designed to characterize further these effects and to examine the site of action for the behavioral actions of hypertonic saline by using central and peripheral administration of less lipophilic AVP antagonists. Further studies are designed to explore the neural site of action for the behavioral effects of central nervous systems (CNS) AVP by using local intracerebral injection of AVP and AVP antagonists. Behavioral tests will include both aversively and appetitively motivated tasks for measuring learning and memory such as active and inhibitory avoidance, a water finding task and a social memory task. Studies also have been designed to explore the functional role of extrahypothalamic and hypothalamic-pituitary AVP by stimulation of AVP cell bodies in the paraventricular nucleus, bed nucleus of the stria terminalis and amygdala and measuring the effects on release of AVP using push-pull cannulation of AVP terminal regions. Subsequently stimulation effective in releasing endogenous central or pituitary AVP will be used to mimic the effects of AVP on behavior. Oxytocin, the second neurohypophyseal nonapeptide, has been reported to have behavioral actions opposite to that of AVP. We propose to extend these earlier observations by characterizing the behavioral effects of both systemically and centrally administered oxytocin and by exploring its mechanism and site of action using oxytocin antagonist peptides. This basic research directed at understanding the mechanism of action for the effects of AVP and oxytocin has important implications, not only for our understanding of the organization of CNS-pituitary interactions in behavioral responses to homeostatic challenge, but also for our understanding of the biological basis of memory and learning.